Fluoxetine effects on hippocampal synaptic connectivity and PSA-NCAM dependent remodelling in an experimental model of depression

PODESTÁ MF, LORENZO LOPEZ JR, CODAGNONE M, LÓPEZ M, BRUSCO A, WIKINSKI S, REINÉS, A

Rosario, Santa Fe, Argentina

Congreso; Congreso.Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE). 2009; 2009

SAFE

Dysfunction of hippocampal plasticity and excessive glutamate (GLU) release has been proposed to play a critical role in the pathophysiology of depression. We examined the synapse morphology and cell adhesion molecule (CAM) expression in the learned helplessness (LH) paradigm, with and without fluoxetine (FLX) treatment. CA3 synapses of LH animals showed increased synaptic cleft width, postsynaptic density (PSD) remodelling and modified synaptic vesicles number compatible with plastic and synaptic connectivity alterations. CA3 NCAM and PSA-NCAM levels diminished in LH rats. GLU hyperstimulation of hippocampal neurons in culture decreased NCAM and PSA-NCAM immunostaining, diminished PSD-95(+) and SYN(+) synapse number and increased SYN(+) individual synapse area, changes that resemble those observed in LH animals. FLX treatment of LH rats recovered synaptic cleft width values, increased reserved synaptic vesicle number, strongly reduced NCAM and increased PSA-NCAM levels in CA3. Results support the hypothesis that GLU hyperactivity in the CA3 of LH rats could reduce CAM expression and that FLX action could involve PSA-NCAM dependent synaptic remodelling that might lead to neuronal connectivity normalization